Coregistered fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) has shown potential to improve the accuracy of radiation targeting of head and neck cancer (HNC) when compared to the use of CT simulation alone. The objective of this study was to identify textural features useful in distinguishing tumor from normal tissue in head and neck via quantitative texture analysis of coregistered 18F-FDG PET and CT images. Abnormal and typical normal tissues were manually segmented from PET/CT images of 20 patients with HNC and 20 patients with lung cancer. Texture features including some derived from spatial grey-level dependence matrices (SGLDM) and neighborhood gray-tone-difference matrices (NGTDM) were selected for characterization of these segmented regions of interest (ROIs). Both K nearest neighbors (KNNs) and decision tree (DT)-based KNN classifiers were employed to discriminate images of abnormal and normal tissues. The area under the curve (AZ) of receiver operating characteristics (ROC) was used to evaluate the discrimination performance of features in comparison to an expert observer. The leave-one-out and bootstrap techniques were used to validate the results. The AZ of DT-based KNN classifier was 0.95. Sensitivity and specificity for normal and abnormal tissue classification were 89% and 99%, respectively. In summary, NGTDM features such as PET Coarseness, PET Contrast, and CT Coarseness extracted from FDG PET/CT images provided good discrimination performance. The clinical use of such features may lead to improvement in the accuracy of radiation targeting of HNC.